title: Synthesis and proteasome inhibition of lithocholic acid derivatives.
abstract: A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic acid hemiester derivative (13) displayed the most potent proteasome inhibition with IC(50) = 1.9 μM. Enzyme kinetic analysis indicates that these lithocholic acid derivatives are noncompetitive inhibitors of the proteasome.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Dang
authors.forename: Andrew
authors.initials: A
authors.lastname: Lin
authors.forename: Phong
authors.initials: P
authors.lastname: Ho
authors.forename: Dominique
authors.initials: D
authors.lastname: Soroka
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Chen
mesh_terms: D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008095:Lithocholic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors
chemical_list: D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D008095:Lithocholic Acid; D046988:Proteasome Endopeptidase Complex